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As Ebola outbreak grows, question of using vaccine becomes more urgent

mantouchong

2017-05-19

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A hospital worker in Conakry in 2015 opted to receive the experimental VSV Ebola vaccine.

Idrissa SOUMARE/Afreecom

As Ebola outbreak grows, question of using vaccine becomes more urgent

As health officials and aid workers head to a remote corner of the Democratic Republic of the Congo to respond to an outbreak of Ebola virus disease, a key question remains: Will the government authorize the use of a promising experimental vaccine? The vaccine had stunning results in a clinical trial in Guinea in 2015, but it has yet to be licensed for broad use.

As DRC officials weigh whether to use the vaccine, new details are emerging about the outbreak, which so far includes 20 suspected cases and three deaths, including the first, or “index,” case. Most cases are in the Bas-Uélé health zone that borders the Central African Republic. Three teams there are working on identifying suspect cases, educating the communities, and investigating villages where “nonsecure” funerals have taken place. They are also contacting a traditional healer in Nambwa who “received the index case”—a 45-year-old man who first sought help on 22 April—for 6 days.

In Likati, the largest town in the area, another team is overseeing a database of the cases. Two mobile laboratories are on their way, as are personal protective equipment for frontline responders, reagents for 100 tests, and GPSs for field crews. More experts from the government, the World Health Organization (WHO), Doctors Without Borders (MSF), and the Alliance for International Medical Action are on the way, and a helicopter is being arranged to bridge Likati to other places.

A WHO situation report issued 16 May ups the ante further: It says health workers are following about 400 close contacts of cases—a jump from 125 in the report from the day before. And one of the latest suspected cases inexplicably is several hundred kilometers from the confirmed outbreak—in the Haut-Uélé province that borders South Sudan.

Some experts question why DRC officials have been slow to request deployment of the vaccine. WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) met 25–27 April and, in meeting notes that are publicly available, explicitly spells out recommendations for deploying the still-unlicensed Ebola vaccine, technically known as rVSVΔG-ZEBOV-GP. The vaccine is manufactured by Merck, which has some 700,000 doses on ice in the United States. According to SAGE recommendations, the vaccine should “be promptly deployed” if a confirmed case of Ebola occurs that matches the Zaire strain used to make the vaccine—which is the case in the DRC (two cases have been confirmed to date). Given that it’s unlicensed, the vaccine must be used in a clinic study, and SAGE specifically suggests countries use the same “ring vaccination” design used in the Guinea trial that vaccinates people who came in contact with cases, and frontline responders like doctors, nurses, and funeral staff.

Epidemiologist Michael Osterholm, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis, says the DRC—and every country at risk of Ebola virus—should have approved the use of the vaccine months ago and it should be given to contacts and frontline responders as soon as possible. Osterholm co-chaired a group of experts known as Team B that in January published a report, Completing Development of Ebola Vaccines, that warned that critical gaps stood in the way of using rVSVΔG-ZEBOV-GP before it receives approval.

We want the initial response to be overwhelming so we never give an outbreak a chance to do what it did in West Africa.

Michael Osterholm, University of Minnesota

“This gets down to granular planning,” Osterholm says. “We want the initial response to be overwhelming so we never give an outbreak a chance to do what it did in West Africa. We want to throw everything at it in a reasonable way and a vaccine is part of that.”

Marie-Paule Kieny, a WHO assistant director-general who oversaw the agency’s response to the Ebola epidemic that raged through West Africa in 2014–16, on 17 May spoke with ScienceInsider about the question of whether the vaccine will be used. Kieny, who is based in Geneva, Switzerland, is not heading the response to this outbreak, but has a long history of coordinating responses to outbreaks of infectious diseases and deploying vaccines. The interview has been edited for clarity and brevity.

Q: Do you have any concern about there being a delay in the process regardless of whether the vaccine is used?

A: WHO is strongly in favor of using the vaccine in conjunction with the other interventions available. That said, the rVSV-ZEBOV Ebola vaccine is not yet available commercially, because it is still under review by the U.S. Food and Drug Administration and other regulatory agencies. In these circumstances the Ebola vaccine can only be used in a study protocol that includes ethical oversight and informed consent of individuals who agree to receive the vaccine. Vaccine use needs to be in compliance with Good Clinical Practice, in order to maximize opportunities to gather additional information on vaccine safety, efficacy, and effectiveness. Governments also must assess their need for the vaccine and their ability to deploy it. The DRC government wants to have a better understanding of the situation before deciding whether, in view of the logistical difficulties, they’d rather concentrate on classical containment control, which has always been successful in this country. You shouldn’t underestimate the logistical challenge [of doing] a vaccination study in a place that is very difficult to access.

Q: WHO doesn’t have the power to enforce anything and is just making a recommendation. Is what the DRC government is doing different from the recommendation?

A: This SAGE recommendation is very recent, and the full report of the SAGE meeting that came to this recommendation has not yet been published. In addition, DRC has already successfully managed seven Ebola outbreaks without a vaccine. So we have the combination of a new recommendation, a new vaccine not yet registered, and the substantial experience of the country to handle Ebola outbreaks. The government will determine the course that is most appropriate for them in this situation.

Q: If the DRC decides 1 week from now they want to do a vaccine study, will they still have to complete a number of steps that would further delay deployment?

A: Actions are already being undertaken that would shorten the timeline. We know already which vaccine would be shipped. All the documentation is ready. Cold chain equipment to maintain the vaccine at –80°C in Kinshasa is in place, so the vaccine could be stored properly in the capital if it were to be imported. In order to transport the vaccine to the field they could use ARKTEK containers, a technology developed with funding from the [Bill & Melinda] Gates Foundation that uses kerosene packs instead of ice packs to keep the vaccine at very low temperature. They are not available yet in DRC, but WHO has received them from the government of Guinea, which is happy to provide ones they used in the Ebola ring vaccination trial.

Once the determination has been made to use the vaccine, it is likely to take only 2 days to ship the vaccine to Kinshasa. From there to the field will not be an easy trip. Material may need to be transported by helicopter. There are some roads, but trees often block them, so the only way is going with motorcycle. This is good in terms of slowing down transmission because this is not a highway—you have less mixing of populations. But it does not make it easy in terms of intervention.

Q: Are you concerned that a delay in the decision by the government to say yes might cause delays somewhere along the way?

A: The key issue to keep in mind is that the actions happening already—the epidemiological investigation, the contact monitoring, the social mobilization, improving access through direct flights for supplies, the people going to the field—are all part of the response needed if there is a vaccination campaign. And the other parts, such as working with the vaccine manufacturer and working with the country’s regulator, we are also already working on.

Q: A clock is ticking.

A: I do agree the clock is ticking. But honestly speaking, I don’t think the time is wasted because everything has been moving in parallel. In terms of operation, time hasn’t been lost because there needs to be a lot of preparation.

Q: How many doses of the vaccine leftover from the Guinea trial are in Geneva?

A: We still have 240 vials, which were re-exported out of Guinea. Each vial has four doses, so it’s a bit less than 1000 doses.

Q: The frontline responders may or may not be from the DRC. They of course are highly vulnerable. Has there been a discussion about offering them vaccine?

A: For the time being, we are still waiting on the decision of whether to move or not on vaccines. There’s a plan to offer them the vaccine. In the trial in Guinea, none of the MSF or WHO staff who administered the vaccine was vaccinated—although others did get the vaccine, as participants in a study in Geneva, myself included. Now, because there are results, we think there’d be more willingness to be vaccinated.

Q: In the past in the DRC, health care workers have always become sick and died. They’ve contained it but at a huge cost.

A: True, but now we have more materials, more personal protective equipment in place, than we had early on with the West Africa Ebola outbreak.

Q: But it’s not either/or—conventional containment or vaccinate?

A: Of course all options should be considered. WHO and its partners are supporting the Ministry of Health in all areas of the response, including epidemiological assessment, surveillance, logistics and supplies, communications, and community engagement. We are confident in the government’s experience and ability to respond, while providing the support that is needed. We have learned to never underestimate this virus.

With reporting by Gretchen Vogel.

A hospital worker in Conakry in 2015 opted to receive the experimental VSV Ebola vaccine.

Idrissa SOUMARE/Afreecom

As Ebola outbreak grows, question of using vaccine becomes more urgent

As health officials and aid workers head to a remote corner of the Democratic Republic of the Congo to respond to an outbreak of Ebola virus disease, a key question remains: Will the government authorize the use of a promising experimental vaccine? The vaccine had stunning results in a clinical trial in Guinea in 2015, but it has yet to be licensed for broad use.

As DRC officials weigh whether to use the vaccine, new details are emerging about the outbreak, which so far includes 20 suspected cases and three deaths, including the first, or “index,” case. Most cases are in the Bas-Uélé health zone that borders the Central African Republic. Three teams there are working on identifying suspect cases, educating the communities, and investigating villages where “nonsecure” funerals have taken place. They are also contacting a traditional healer in Nambwa who “received the index case”—a 45-year-old man who first sought help on 22 April—for 6 days.

In Likati, the largest town in the area, another team is overseeing a database of the cases. Two mobile laboratories are on their way, as are personal protective equipment for frontline responders, reagents for 100 tests, and GPSs for field crews. More experts from the government, the World Health Organization (WHO), Doctors Without Borders (MSF), and the Alliance for International Medical Action are on the way, and a helicopter is being arranged to bridge Likati to other places.

A WHO situation report issued 16 May ups the ante further: It says health workers are following about 400 close contacts of cases—a jump from 125 in the report from the day before. And one of the latest suspected cases inexplicably is several hundred kilometers from the confirmed outbreak—in the Haut-Uélé province that borders South Sudan.

Some experts question why DRC officials have been slow to request deployment of the vaccine. WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) met 25–27 April and, in meeting notes that are publicly available, explicitly spells out recommendations for deploying the still-unlicensed Ebola vaccine, technically known as rVSVΔG-ZEBOV-GP. The vaccine is manufactured by Merck, which has some 700,000 doses on ice in the United States. According to SAGE recommendations, the vaccine should “be promptly deployed” if a confirmed case of Ebola occurs that matches the Zaire strain used to make the vaccine—which is the case in the DRC (two cases have been confirmed to date). Given that it’s unlicensed, the vaccine must be used in a clinic study, and SAGE specifically suggests countries use the same “ring vaccination” design used in the Guinea trial that vaccinates people who came in contact with cases, and frontline responders like doctors, nurses, and funeral staff.

Epidemiologist Michael Osterholm, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis, says the DRC—and every country at risk of Ebola virus—should have approved the use of the vaccine months ago and it should be given to contacts and frontline responders as soon as possible. Osterholm co-chaired a group of experts known as Team B that in January published a report, Completing Development of Ebola Vaccines, that warned that critical gaps stood in the way of using rVSVΔG-ZEBOV-GP before it receives approval.

We want the initial response to be overwhelming so we never give an outbreak a chance to do what it did in West Africa.

Michael Osterholm, University of Minnesota

“This gets down to granular planning,” Osterholm says. “We want the initial response to be overwhelming so we never give an outbreak a chance to do what it did in West Africa. We want to throw everything at it in a reasonable way and a vaccine is part of that.”

Marie-Paule Kieny, a WHO assistant director-general who oversaw the agency’s response to the Ebola epidemic that raged through West Africa in 2014–16, on 17 May spoke with ScienceInsider about the question of whether the vaccine will be used. Kieny, who is based in Geneva, Switzerland, is not heading the response to this outbreak, but has a long history of coordinating responses to outbreaks of infectious diseases and deploying vaccines. The interview has been edited for clarity and brevity.

Q: Do you have any concern about there being a delay in the process regardless of whether the vaccine is used?

A: WHO is strongly in favor of using the vaccine in conjunction with the other interventions available. That said, the rVSV-ZEBOV Ebola vaccine is not yet available commercially, because it is still under review by the U.S. Food and Drug Administration and other regulatory agencies. In these circumstances the Ebola vaccine can only be used in a study protocol that includes ethical oversight and informed consent of individuals who agree to receive the vaccine. Vaccine use needs to be in compliance with Good Clinical Practice, in order to maximize opportunities to gather additional information on vaccine safety, efficacy, and effectiveness. Governments also must assess their need for the vaccine and their ability to deploy it. The DRC government wants to have a better understanding of the situation before deciding whether, in view of the logistical difficulties, they’d rather concentrate on classical containment control, which has always been successful in this country. You shouldn’t underestimate the logistical challenge [of doing] a vaccination study in a place that is very difficult to access.

Q: WHO doesn’t have the power to enforce anything and is just making a recommendation. Is what the DRC government is doing different from the recommendation?

A: This SAGE recommendation is very recent, and the full report of the SAGE meeting that came to this recommendation has not yet been published. In addition, DRC has already successfully managed seven Ebola outbreaks without a vaccine. So we have the combination of a new recommendation, a new vaccine not yet registered, and the substantial experience of the country to handle Ebola outbreaks. The government will determine the course that is most appropriate for them in this situation.

Q: If the DRC decides 1 week from now they want to do a vaccine study, will they still have to complete a number of steps that would further delay deployment?

A: Actions are already being undertaken that would shorten the timeline. We know already which vaccine would be shipped. All the documentation is ready. Cold chain equipment to maintain the vaccine at –80°C in Kinshasa is in place, so the vaccine could be stored properly in the capital if it were to be imported. In order to transport the vaccine to the field they could use ARKTEK containers, a technology developed with funding from the [Bill & Melinda] Gates Foundation that uses kerosene packs instead of ice packs to keep the vaccine at very low temperature. They are not available yet in DRC, but WHO has received them from the government of Guinea, which is happy to provide ones they used in the Ebola ring vaccination trial.

Once the determination has been made to use the vaccine, it is likely to take only 2 days to ship the vaccine to Kinshasa. From there to the field will not be an easy trip. Material may need to be transported by helicopter. There are some roads, but trees often block them, so the only way is going with motorcycle. This is good in terms of slowing down transmission because this is not a highway—you have less mixing of populations. But it does not make it easy in terms of intervention.

Q: Are you concerned that a delay in the decision by the government to say yes might cause delays somewhere along the way?

A: The key issue to keep in mind is that the actions happening already—the epidemiological investigation, the contact monitoring, the social mobilization, improving access through direct flights for supplies, the people going to the field—are all part of the response needed if there is a vaccination campaign. And the other parts, such as working with the vaccine manufacturer and working with the country’s regulator, we are also already working on.

Q: A clock is ticking.

A: I do agree the clock is ticking. But honestly speaking, I don’t think the time is wasted because everything has been moving in parallel. In terms of operation, time hasn’t been lost because there needs to be a lot of preparation.

Q: How many doses of the vaccine leftover from the Guinea trial are in Geneva?

A: We still have 240 vials, which were re-exported out of Guinea. Each vial has four doses, so it’s a bit less than 1000 doses.

Q: The frontline responders may or may not be from the DRC. They of course are highly vulnerable. Has there been a discussion about offering them vaccine?

A: For the time being, we are still waiting on the decision of whether to move or not on vaccines. There’s a plan to offer them the vaccine. In the trial in Guinea, none of the MSF or WHO staff who administered the vaccine was vaccinated—although others did get the vaccine, as participants in a study in Geneva, myself included. Now, because there are results, we think there’d be more willingness to be vaccinated.

Q: In the past in the DRC, health care workers have always become sick and died. They’ve contained it but at a huge cost.

A: True, but now we have more materials, more personal protective equipment in place, than we had early on with the West Africa Ebola outbreak.

Q: But it’s not either/or—conventional containment or vaccinate?

A: Of course all options should be considered. WHO and its partners are supporting the Ministry of Health in all areas of the response, including epidemiological assessment, surveillance, logistics and supplies, communications, and community engagement. We are confident in the government’s experience and ability to respond, while providing the support that is needed. We have learned to never underestimate this virus.